Valve translocation device and method for the treatment of functional valve

ABSTRACT

The present invention provides devices for treating functional mitral regurgitation and methods of use thereof. The devices translocate a subject&#39;s mitral valve in an apical direction. The devices thereby treat mitral regurgitation while preserving a subject&#39;s original mitral valve and chordae tendinae.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.17/584,157, filed on Jan. 25, 2022, which is a continuation of U.S.patent application Ser. No. 16/888,322 filed on May 29, 2020, whichissued as U.S. Pat. No. 11,259,925 on Mar. 1, 2022, which is acontinuation of International Application No. PCT/US20/31110, filed May1, 2020, which claims priority to U.S. Provisional Application No.62/842,085, filed May 2, 2019, the disclosures of each of which arehereby incorporated by reference herein in their entirety. Further, U.S.patent application Ser. No. 17/584,157 is a continuation-in-part of U.S.patent application Ser. No. 16/761,181 filed on May 1, 2020, which is aUS national entry of International Application No. PCT/US18/59253, filedNov. 5, 2018, which claims priority to U.S. Provisional PatentApplication No. 62/581,085, filed Nov. 3, 2017, the disclosures of whichare each hereby incorporated by reference herein in their entirety

BACKGROUND OF THE INVENTION

There is presently no reliable, durable mitral valve repair option forpatients with functional mitral regurgitation (FMR). In patients withFMR, the mitral valve is usually normal, but left ventriculardysfunction (due to coronary artery disease, idiopathic myocardialdisease, or nonischemic cardiomyopathy) is present. The abnormal anddilated left ventricle causes papillary muscle displacement, whichresults in leaflet tethering with associated annular dilation thatprevents coaptation (generally defined as abutment of the edges of thetwo mitral valve leaflets). Thus, fundamental geometric issues of FMRinclude annular dilation, annular flattening, leaflet tethering, andincreased interpapillary distances.

Although restrictive mitral annuloplasty (RMA) is usually initiallyeffective in abrogating mitral regurgitation, there is clear data thatthese repairs are not as durable as replacing the mitral valve with aprosthetic (tissue or mechanical) valve. RMA involves suturing asemi-rigid ring around the perimeter of the mitral valve (the annulus)to decrease the area of the mitral orifice and increase the amount ofcoaptation of the two leaflets. The frequent progressive ineffectivenessof RMA is generally due to continued adverse remodeling and enlargementof the left ventricle, with continued geometric distortion—includingcontinued restriction of the leaflets into the ventricular cavity withresulting failure of coaptation.

For example, in the ACORN trial (see J Thorac Cardiovasc Surg. 2011September; 142(3):569-74) that included mostly patients with idiopathicFMR, the recurrence rate of severe mitral regurgitation (MR) was 19percent at 5 years. Recent data from a randomized trial that comparedrepair and replacement of the mitral valve for severe FMR demonstratedthat nearly 60 percent of patients with mitral valve repairs orreplacements suffered recurrence of moderate or greater MR at 2 years.Importantly, the group of patients with recurrence also showed lessfavorable ventricular reverse remodeling (i.e. they had biggerventricles) compared to a repair group that had durable treatment of MR.Fundamentally, a restrictive mitral annuloplasty does not leave anadequate surface area for coaptation. A variety of techniques have beentried to repair FMR in a more durable fashion than current techniques,but none have had widespread adoption or success.

While replacing the mitral valve with a prosthetic valve is the mostdurable current technique, prosthetic valves have significant downsides,including risks of thromboembolism, prosthetic valve infection,degeneration of bioprostheses, mandatory anticoagulation of mechanicalvalves, and a higher perioperative mortality risk. While there are clearbenefits to mitral valve repair compared to replacement for patientswith degenerative mitral valve disease, annuloplasty insertion fortreating FMR is associated with a very high rate of early recurrence ofmitral regurgitation (e.g., 58% at two years in a randomized CTSN trial,NEJM 2016).

Common techniques often use a MitraClip®, and are based on a surgicalapproach (the “Alfieri” stitch) that is known to be only variablyeffective. The MitraClip® procedure involves placing a Dacron®-coveredtitanium clip such that the middle portion of the anterior and posteriorleaflets are joined, which forms the mitral valve into a “doubleorifice” valve. Results from treatment of FMR with the MitraClip® havebeen suboptimal and a substantial number of patients have eitherresidual or recurrent mitral regurgitation.

Therefore, there is a need in the art for improved devices and methodsfor treating functional mitral regurgitation. The present inventionaddresses this need.

SUMMARY OF THE INVENTION

In some embodiments, an apparatus comprises a ring-shaped body having anannulus portion and a leaflet portion axially spaced from the annulusportion, the annulus portion having an annulus end having a perimeterand being configured to be attached to an annulus of a native heartvalve from which a leaflet of the native heart valve has been separated,the leaflet portion having a leaflet end having a perimeter equal to orlarger than the annulus portion perimeter and being configured to beattached to the native heart valve leaflet and thereby to connect thenative heart valve leaflet to the native heart valve annulus.

In some embodiments, the leaflet portion of the ring-shaped bodyincludes a pleat having an expandable portion extending to the leafletend of the ring-shaped body to define in part the perimeter of theleaflet end and a fixed portion spaced from the leaflet end, theexpandable portion of the pleat being configured to be attached to thenative heart valve leaflet.

In some embodiments, the pleat is a first pleat, the expandable portionof the first pleat is configured to be attached to the leaflet, theleaflet portion of the ring-shaped body includes a second pleat havingan expandable portion extending to the leaflet end of the ring-shapedbody further to define in part the perimeter of the leaflet end and afixed portion spaced from the leaflet end, the expandable portion of thesecond pleat being configured to be attached to the leaflet.

In some embodiments, the leaflet end of the ring-shaped body has a firstcircumferential portion having a thickness and a second circumferentialportion have a thickness different from the thickness of the firstcircumferential portion.

In some embodiments, the native heart valve leaflet is a first leafletfrom a plurality of native heart valve leaflets that have been separatedfrom the native heart valve, the first leaflet having a first thicknessand a second leaflet from the plurality of native heart valve leafletshaving a second thickness, the first thickness being greater than thesecond thickness, and the thickness of the first circumferential portionbeing approximately equal to the first thickness and the thickness ofthe second circumferential portion being approximately equal to thesecond thickness.

In some embodiments, the native heart valve is a mitral valve, the firstleaflet is an anterior leaflet and the second leaflet is a posteriorleaflet.

In some embodiments, the annulus end has a thickness greater than athickness of the remainder of the annulus portion.

In some embodiments, the annulus portion is formed of a sheet ofmaterial, the annulus end is integrally formed with the remainder of theannulus portion with multiple layers of the sheet of material.

In some embodiments, the annulus end is formed by rolling the sheet ofmaterial.

In some embodiments, the annulus end is formed separately from, andcoupled to, the annulus portion.

In some embodiments, the ring-shaped body is formed of biologicaltissue.

In some embodiments, the biological tissue is human or bovinepericardial tissue.

In some embodiments, the ring-shaped body is formed of at least one ofdecellularized tissue, polymer, or artificial fabric.

In some embodiments, the annulus portion has a thickness different fromthe leaflet portion.

In some embodiments, a method of repairing a native heart valve having anative annulus and native leaflets extending from the native annulus,comprises separating a native leaflet from the native annulus, theseparated native leaflet having an annulus edge at which the nativeleaflet was joined to the annulus and the native annulus having aleaflet edge at which the annulus was joined to the leaflet edge of thenative leaflet; attaching to the leaflet edge of the native annulus anannulus end of an annulus portion of a ring-shaped body, the annulus endhaving a perimeter; and attaching to the annulus edge of the nativeleaflet a leaflet end of a leaflet portion of the ring-shaped body, theleaflet portion being axially spaced from the annulus portion, theleaflet end having a perimeter equal to or larger than the perimeter ofthe annulus end.

In some embodiments, the native leaflet is circumferentially redundantin configuration, the leaflet portion of the ring-shaped body includes apleat having an expandable portion extending to the leaflet end of thering-shaped body and a fixed portion spaced from the leaflet end, andthe attaching to the annulus edge of the native leaflet includescircumferentially expanding the native leaflet and attaching theexpandable portion of the pleat to the native leaflet.

In some embodiments, the native leaflet is a first native leaflet andthe separating includes separating a second native leaflet from thenative annulus, the separated second native leaflet having an annulusedge at which the second native leaflet was joined to the annulus, thesecond native leaflet being segmented, the pleat is a first pleat, andthe leaflet portion of the ring-shaped body includes a second pleathaving an expandable portion extending to the leaflet end of thering-shaped body and a fixed portion spaced from the leaflet end, andthe attaching to the annulus edge including attaching the expandableportion of the second pleat to the second native leaflet.

In some embodiments, the native leaflet is a first native leaflet andthe separating includes separating a second native leaflet from thenative annulus, the first native leaflet having a first thickness andthe second native leaflet having a second thickness, the first thicknessbeing greater than the second thickness, the leaflet end of thering-shaped body has a first circumferential portion having a thicknessapproximately equal to the first thickness and a second circumferentialportion having a thickness less than the thickness of the firstcircumferential thickness and approximately equal to the secondthickness, and the attaching to the annulus edge including attaching thefirst circumferential portion to the first native leaflet and attachingthe second circumferential portion to the second native leaflet.

In some embodiments, the native heart valve is a mitral valve, the firstnative leaflet is an anterior leaflet, and the second native leaflet isa posterior leaflet.

In some embodiments, the attaching to the leaflet edge of the nativeannulus and the attaching to the annulus edge of the native leafletincludes suturing.

In some embodiments, the attaching to the leaflet edge of the nativeannulus includes passing sutures through the annulus end of thering-shaped body, through the native annulus, and through a plurality ofpledgets distributed circumferentially around the native annulus.

In some embodiments, a method of repairing a native heart valve having anative annulus and native leaflets extending from the native annulus,comprising separating a native leaflet from the native annulus, theseparated native leaflet having an annulus edge at which the nativeleaflet was joined to the annulus and the native annulus having aleaflet edge at which the annulus was joined to the leaflet edge of thenative leaflet; attaching to the leaflet edge of the native annulus anannulus end of an annulus portion of a semi-annular body; and attachingto the annulus edge of the native leaflet a leaflet end of a leafletportion of the semi-annular body, the leaflet portion being axiallyspaced from the annulus portion.

In some embodiments, the native leaflet is a first native leaflet from aplurality of native leaflets extending from the native annulus, theattaching to the leaflet edge the annulus end of the annulus portion ofthe semi-annular body occurring with a second native leaflet extendingfrom the native annulus.

In some embodiments, the method further comprises: separating from thenative annulus a third native leaflet from the plurality of nativeleaflets, the third separated native leaflet having an annulus edge atwhich the native leaflet was jointed to the annulus; and attaching tothe annulus edge of the third native leaflet the leaflet end of theleaflet portion of the semi-annular body.

In some embodiments, the separating the native leaflet from the nativeannulus includes separating less than an entirety of the native leafletfrom the native annulus, thereby leaving a portion of the native leafletattached to and extending from the native annulus.

In some embodiments, the portion of the native leaflet attached to andextending from the native annulus is between about 2 mm and about 4 mmin length.

In some embodiments, the native heart valve is a tricuspid valve.

In some embodiments, an apparatus comprises a ring-shaped body having anannulus portion and a leaflet portion axially spaced from the annulusportion, the annulus portion having an annulus end and being configuredto be attached to an annulus of a native heart valve from which aleaflet of the native heart valve has been separated, the leafletportion having a leaflet end including a pleat having an expandableportion extending to the leaflet end and a fixed portion spaced from theleaflet end, the expandable portion of the pleat being configured to beattached to the native heart valve leaflet and thereby to connect thenative heart valve leaflet to the native heart valve annulus.

In some embodiments, the expandable portion of the pleat has a firstconfiguration in which the leaflet end has a first perimeter and asecond, expanded configuration, in which the leaflet end has a secondperimeter greater than the first perimeter.

In some embodiments, the annulus end has a perimeter, and the leafletend has a perimeter equal to or greater than the annulus end perimeterwhen the expandable portion of the pleat is in its second, expandedconfiguration.

In some embodiments, the annulus end has a perimeter, and the leafletend has a perimeter less than the annulus end perimeter when theexpandable portion of the pleat is in its second, expandedconfiguration.

In some embodiments, a translocation collar device comprises asubstantially ring-shaped band of material having a first edge, a secondedge opposite from the first edge, and a width in between; wherein thecollar device is attachable to a circumferentially separated valve suchthat the first edge is attached to a valve annulus and the second edgeis attached to a valve perimeter to translocate the valve in an apicaldirection.

In some embodiments, the first edge or the second edge has a diameterbetween about 20 mm and 60 mm.

In some embodiments, the width is between about 5 mm and 15 mm.

In some embodiments, the width is biased such that the first edge andthe second edge are separated by a variable distance.

In some embodiments, the device is constructed from a length of materialhaving an arc shape, with a first end, a second end, an outer arc, andan inner arc, such that the first end and the second end are joinabletogether to form a substantially ring-shaped band.

In some embodiments, the device further comprises one or more concentricfolds aligned in parallel with the first edge and the second edge, suchthat the width is variable.

In some embodiments, the width is fixable by applying one or moresutures or adhesives to the one or more concentric folds.

In some embodiments, the device further comprises one or moreannuloplasty rings attached to the annular edge, the apical edge, orboth.

In some embodiments, the device further comprises one or more cuffsattached to the first edge, the second edge, or a position in between.

In some embodiments, the material is selected from the group consistingof: polymer, fabrics, plastics, metals, autograft tissue, allografttissue, xenograft tissue, and engineered tissue constructs.

In some embodiments, one of the first edge and the second edge is rolledto form a sewing cuff or collar.

In some embodiments, the ring-shaped band of material comprises one ormore pleats extending from the first edge to the second edge.

In some embodiments, at least one flap of material extends from one ofthe first edge and the second edge to form at least one neo-leaflet.

In some embodiments, a plurality of artificial chords are looped alongan outer edge of the at least one flap of material and the edge that theat least one flap of material extends from.

In some embodiments, a method of translocating a valve, the methodcomprises the steps of providing a translocation collar device having aring-like shape with a first edge, a second edge, and a width inbetween; forming a circumferential incision around a perimeter of avalve to separate a valve annulus from a valve perimeter;circumferentially attaching the first edge of the collar device to thevalve annulus; and circumferentially attaching the second edge of thecollar device to the valve perimeter.

In some embodiments, the translocation collar device is sized to fit thevalve annulus and valve perimeter by measuring the dimensions of thevalve annulus and valve perimeter.

In some embodiments, the translocation collar device is sized to fit thevalve annulus and valve perimeter by performing and measuring thedimensions of a 3D echocardiogram of a heart containing the valve.

In some embodiments, the circumferential incision is formed whilekeeping the valve and associated structures intact, the associatedstructures including leaflets, commissures, chordae tendinae, andpapillary muscles.

In some embodiments, the first edge and the second edge of the collardevice are attached after the circumferential incision is fully formedand the valve annulus is completely separated from the valve perimeter.

In some embodiments, the first edge and the second edge of the collardevice are attached as the circumferential incision is being formed andthe valve annulus is partially separated from the valve perimeter.

In some embodiments, a valve translocation kit, comprises at least onetranslocation collar device having a ring-like shape with a first edge,a second edge, and a width in between; and one or more suture threads,suture pledgets, forceps, scissors, scalpels, translocation collardevice holders, and combinations thereof.

In some embodiments, the kit further comprises one or morecircumferential bands, each circumferential band configured to wraparound papillary muscles connected to a valve.

In some embodiments, the kit further comprises one or more tethers orartificial chords.

BRIEF DESCRIPTION OF THE DRAWINGS

The following detailed description of embodiments of the invention willbe better understood when read in conjunction with the appendeddrawings. It should be understood, however, that the invention is notlimited to the precise arrangements and instrumentalities of theembodiments shown in the drawings.

FIG. 1 is a front view schematic illustration of a native heart valve.

FIG. 2 is a front view schematic illustration of a valve translocationdevice, according to an embodiment.

FIG. 3 is a front view schematic illustration of the valve translocationdevice of FIG. 2 deployed within the native heart valve of FIG. 1 .

FIG. 4 is an opened and flattened view of the valve translocation deviceof FIG. 2 deployed within the native heart valve.

FIG. 5A is a flowchart illustrating a method of deploying a valvetranslocation device to a desired location in a body, according to anembodiment.

FIG. 5B is a flowchart illustrating a method of deploying a valvetranslocation device to a desired location in a body, according to anembodiment.

FIG. 6A and FIG. 6B depict in front cross-sectional view the anatomy ofa left atrium, left ventricle, and mitral valve, in an open and closedconfiguration, respectively. FIG. 6C depicts an exemplary translocationcollar device and the implantation of the translocation collar devicearound the mitral valve to displace it towards the apex of the heart,according to an embodiment.

FIG. 7A and FIG. 7B depict exemplary translocation collar devices havingbiased heights.

FIG. 8A through FIG. 8C depict exemplary translocation collar deviceshaving annuloplasty rings.

FIG. 9A through FIG. 9C depict exemplary translocation collar deviceshaving adjustable heights.

FIG. 10A through FIG. 10C depict exemplary translocation collar deviceshaving sewing cuffs.

FIG. 11A through FIG. 11D depict the progression of the formation of anexemplary translocation collar device. FIG. 11A shows a full template.FIG. 11B shows the top portion of the template rolled over twice to formthe sewing cuff or collar. Markings on the template and patch showquadrants (unbroken lines) and eighth marks (dashed lines), which aretranscribed onto the template. FIG. 11C shows the completed sewing cuffor collar on template; red indicates running suture to secure the rollededge to the body of the device. Dashed lines are original templateoutline.

FIG. 12 is a photograph showing the rolled sewing cuff or collar of anexemplary translocation collar device after it has been completed butbefore it is ready to be implanted. The device must then be sewnend-to-end into a cylinder/frustrum shape. Markings on the device shownquadrants (unbroken lines) and eighth marks (dashed lines). Thesemarkings facilitate proper orientation and suturing of the device to thenative mitral annulus and native mitral valve.

FIG. 13 is a photograph (top) shows the rolled sewing cuff or collar ofan exemplary translocation collar device ready for suturing and aschematic of the rolled sewing cuff or collar and a pledget supporting asuture (bottom).

FIG. 14 is a photograph showing the use of an interrupted pledgetedhorizontal mattress suture line using relatively small pledgets.

FIG. 15 is a photograph showing an exemplary translocation collar devicemounted on a rigid circular holder, in order to facilitate suturing ofthe device. In this example, a mitral annuloplasty ring has been used asthe rigid circular holder.

FIG. 16 is a photograph showing the placement of the pledgeted stitchesthrough the sewing cuff of an exemplary translocation collar device.

FIG. 17 is a photograph showing the translocation collar device seateddown into the annulus of the valve once all stitches are placed.

FIG. 18 is a photograph showing the holder removed, all pledgetedstitches tied, and the translocation collar device naturally invertingwhen pushed down into the ventricle. At this point the native mitralleaflets can be sewn to the bottom (free edge) of the device.

FIG. 19 is a photograph showing that the native mitral valve ischaracterized by “clefts” between portions of the posterior leaflet.

FIG. 20A through FIG. 20I depict the progression of the formation of anexemplary translocation collar device. FIG. 20A shows the full template;the device is drawn on to a pericardium, transferring all marks from thetemplate to the pericardium. The ‘X’ and ‘x’ notations indicate thelocations of the three pleats. The upper ‘X’ is located in the area thatwill be rolled/cuffed, and the lower ‘x’ is in the patch proper thatwill be pleated. FIG. 20B shows the creation of a pleat, where the areas‘X’ are cut out of the pericardium, leaving the areas ‘x’ intact. FIG.20C shows the ‘x’ portions are folded over such that the cut edges(where the ‘X’ portions were removed) line up (at the halfway point ofthe ‘x’ portion on the patch). The pleat is sewn in place using runningprolene suture (red hash marks). This is done for all pleats in thedevice. FIG. 20D shows three pleats have been created. The ‘x’ portionsare ‘hidden’ inside the pleat, shown as triangles in the body of thepatch, secured by the stitches at the level of the collar (red hashmarks). FIG. 20E shows the sewing collar portion of the device is thenrolled over twice. It can be held in position using clamps while it issewn into place with running prolene suture. FIG. 20F shows thecompleted patch, showing the rolled edge of the sewing collar has beenstitched down (red hash marks). Figure-of-eight stitches are placed atthe juncture between pleats where the ‘X’ portions were removed, so asto prevent leaks. Grey dashed lines show the original template shape.FIG. 20G shows the completed pleated device. FIG. 20H shows thecompleted frustrum-shaped device in 3D. FIG. 20I shows a ruffled devicein 3D.

FIG. 21 shows (top) an exemplary translocation collar device showingcolored marks for alignment and (bottom) tissue below the red line isgiven in order to provide room to attach the inner suture line to thenative mitral valve—this can be left long and trimmed back as necessary.

FIG. 22A through FIG. 22C depict an exemplary translocation collardevice with pleats prototyped using surgical drape material. FIG. 22Adepicts a completed pleated device (having 4 pleats) mounted to a mitralvalve replacement sizer (left) and unmounted (right) showing the‘anterior leaflet’ portion. FIG. 22B depicts the device mounted to amitral valve sizer (left) and unmounted (middle, right) showing‘posterior leaflet’ portion with pleats. FIG. 22C depicts additionalviews of the unmounted device from the atrial/annular side (left) andthe ventricular/leaflet side (right).

FIG. 23 depicts an exemplary implanted translocation collar device withthe addition of a circumferential band around the chordae tendinae andpapillary muscles.

FIG. 24 depicts an exemplary implanted translocation collar device withthe addition of supplementary tethers connected to the papillarymuscles.

FIG. 25 is a flowchart depicting an exemplary method of implanting atranslocation collar device.

FIG. 26A through FIG. 26E illustrate the steps of implanting anexemplary translocation collar device around a mitral valve.

FIG. 27 is a flowchart depicting an exemplary method configured tofacilitate durable mitral valve repair.

FIG. 28 is a photograph depicting the formation of a translocationcollar patch.

FIG. 29 is a photograph depicting the formation of a ring configured tostiffen the translocation collar patch.

FIG. 30A and FIG. 30B are photographs depicting the coupling of the ringto the translocation collar patch.

FIG. 31A and FIG. 31B are photographs depicting detaching leaflet tissuefrom valve tissue within the heart (e.g., using typical methods) priorto attaching a first end of sutures to the valve tissue.

FIG. 32 is a photograph depicting coupling sutures to the patch bypassing a second end of the sutures through an inner portion of thepatch.

FIG. 33A and FIG. 33B are photographs depicting sliding the patch alongthe sutures to be adjacent to the first end of the sutures.

FIG. 34 through FIG. 38 are photographs depicting securing the patch tothe valve tissue.

FIG. 39 depicts common surgical approaches to treat functional mitralregurgitation, each with its own drawbacks.

FIG. 40A and FIG. 40B depict the implantation of an exemplarytranslocation collar device into an excised porcine heart. The collar issewn circumferentially to the mitral valve (i.e., first/distal sutureline). After the distal suture line is complete, a standard mitralannuloplasty ring is placed around the collar at the level of the sutureline, it is next sewn in place. The annuloplasty ring serves tostabilize and fix the perimeter of the mitral valve in an optimalconfiguration. In the final result, the collar is in place and themitral valve is translocated toward the ventricle.

FIG. 41 depicts three prototype translocation collar devices havingvarying widths.

FIG. 42A and FIG. 42B depict the results of an in vivo swine analysiscomparing the effects of implanting a prototype translocation collardevice on mitral valve coaptation.

FIG. 43A and FIG. 43B depict a modified fabrication process to create aprototype translocation collar device having a steeper angle and sizedto the dimensions of a recipient's annulus.

FIG. 44A and FIG. 44B depict an implanted translocation collar devicehaving an upper diameter of 40 mm and a lower diameter of 28 mm.

FIG. 45A and FIG. 45B depict an implanted translocation collar devicehaving an upper diameter of 32 mm and a lower diameter of 28 mm.

FIG. 46A and FIG. 46B depict the use of non-locking sutures (FIG. 46A)and the use of locking sutures (FIG. 46B) to prevent crimping.

FIG. 47A through FIG. 47D depict a sequence of implanting a prototypetranslocation collar device having 2 mm upper and lower tabs forhorizontal mattress sutures.

FIG. 48 is a schematic illustration of a tricuspid valve, showing thatalthough the base of the anterior and posterior leaflets may dilate, theseptal leaflet may not.

DETAILED DESCRIPTION

The present invention provides devices and techniques for durable andreasonably adaptable valve translocation to repair and treatregurgitation. The device translocates a subject's mitral valve (and/orother heart valve, such as a tricuspid valve) in the ventricle,positioning the mitral valve toward the apex of the subject's heart tocompensate for the fundamental geometric issues of FMR, such as annulardilation, annular flattening, leaflet tethering, and increasedinterpapillary distances. The device is configured to decrease theamount of tethering of the patient's mitral valve leaflets to increasethe coaptation surface area between the two mitral valve leaflets. Thedevice preserves the original mitral valve and chordae tendinae in anintact manner. Therefore, the device increases the likelihood of adurable repair and an effective and lasting treatment of FMR. Inaddition, the device addresses flattening of the annulus and annulardilation.

Definitions

The embodiments herein and the various features and advantageous detailsthereof are explained more fully with reference to the non-limitingembodiments that are illustrated in the accompanying drawings anddetailed in the following description. Descriptions of well-knowncomponents and processing techniques are omitted so as to notunnecessarily obscure the embodiments herein. The examples used hereinare intended merely to facilitate an understanding of ways in which theembodiments herein may be practiced and to further enable those of skillin the art to practice the embodiments herein. Accordingly, the examplesshould not be construed as limiting the scope of the embodiments herein.Rather, these embodiments are provided so that this disclosure will bethorough and complete, and will fully convey the scope of the inventiveconcepts to those skilled in the art. Like numbers refer to likeelements throughout.

Unless defined elsewhere, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the present invention, exemplary methods andmaterials are described.

As used herein, each of the following terms has the meaning associatedwith it in this section.

As used herein, the singular forms “a”, “an” and “the” are intended toinclude the plural forms as well, unless the context clearly indicatesotherwise. With respect to the use of substantially any plural and/orsingular terms herein, those having skill in the art can translate fromthe plural to the singular and/or from the singular to the plural as isappropriate to the context and/or application. The varioussingular/plural permutations may be expressly set forth herein for sakeof clarity.

In general, terms used herein, and especially in the appended claims(e.g., bodies of the appended claims) are generally intended as “open”terms (e.g., the term “including” should be interpreted as “includingbut not limited to,” the term “having” should be interpreted as “havingat least,” etc.). Similarly, the terms “comprises” and/or “comprising,”when used in this specification, specify the presence of statedfeatures, integers (or fractions thereof), steps, operations, elements,and/or components, but do not preclude the presence or addition of oneor more other features, integers (or fractions thereof), steps,operations, elements, components, and/or groups thereof. As used in thisdocument, the term “comprising” means “including, but not limited to.”

As used herein the term “and/or” includes any and all combinations ofone or more of the associated listed items. It should be understood thatvirtually any disjunctive word and/or phrase presenting two or morealternative terms, whether in the description, claims, or drawings,should be understood to contemplate the possibilities of including oneof the terms, either of the terms, or both terms. For example, thephrase “A or B” will be understood to include the possibilities of “A”or “B” or “A and B.”

All ranges disclosed herein also encompass any and all possiblesubranges and combinations of subranges thereof unless expressly statedotherwise. Any listed range should be recognized as sufficientlydescribing and enabling the same range being broken down into at leastequal subparts unless expressly stated otherwise. As will be understoodby one skilled in the art, a range includes each individual member. Forexample, description of a range such as from 1 to 6 should be consideredto have specifically disclosed subranges such as from 1 to 3, from 1 to4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., as well asindividual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5,5.3, 6, and any whole and partial increments therebetween. This appliesregardless of the breadth of the range.

Some biocompatible synthetic material(s) can include, for example,polyesters, polyurethanes, polytetrafluoroethylene (PTFE) (e.g.,Teflon), and/or the like. Where a thin, durable synthetic material iscontemplated, synthetic polymer materials such expanded PTFE orpolyester may optionally be used. Other suitable materials mayoptionally include elastomers, thermoplastics, polyurethanes,thermoplastic polycarbonate urethane, polyether urethane, segmentedpolyether urethane, silicone polyether urethane, polyetheretherketone(PEEK), silicone-polycarbonate urethane, polypropylene, polyethylene,low-density polyethylene (LDPE), high-density polyethylene (HDPE),ultra-high density polyethylene (UHDPE), polyolefins,polyethylene-glycols, polyethersulphones, polysulphones,polyvinylpyrrolidones, polyvinylchlorides, other fluoropolymers,polyesters, polyethylene-terephthalate (PET) (e.g., Dacron),Poly-L-lactic acids (PLLA), polyglycolic acid (PGA), poly(D,L-lactide/glycolide) copolymer (PDLA), silicone polyesters, polyamides(Nylon), PTFE, elongated PTFE, expanded PTFE, siloxane polymers and/oroligomers, and/or polylactones, and block co-polymers using the same.

“About” as used herein when referring to a measurable value such as anamount, a temporal duration, and the like, is meant to encompassvariations of ±20%, ±10%, ±5%, ±1%, and ±0.1% from the specified value,as such variations are appropriate.

Valve Translocation Device

Referring now to FIG. 1 through FIG. 3 , front view schematicillustrations of a native heart valve, a valve translocation device 100,and the valve translocation device 100 deployed within the native heartvalve are shown, respectively, according to some embodiments. FIG. 4 isan opened and flattened view of the valve translocation device 100deployed within the native heart valve.

The valve translocation device 100 (also referred to herein as“translocation device,” “device,” “patch,” and “translocation collardevice”) is configured to be deployed in a heart within a body (e.g., ofa human patient) and to effectively relocate at least a portion of anative heart valve to improve valve function (e.g., optimize valveleaflet coaptation during systole and minimize valve obstruction toblood flow during diastole). More specifically, in use, one or morenative heart valve leaflets that have been detached from the heart canbe coupled to the valve translocation device 100, and the translocationdevice 100 can be attached to the heart to place the native leaflet(s)in a position within the heart different from their native position(e.g., further into the ventricle of the heart). In this manner, forpatients with damaged/dilated ventricles, for example, as discussed infurther detail herein, moving at least a portion of the valve towardsthe ventricle can improve overall valve function.

As shown in FIG. 1 , a native heart valve sits between an atrium and aventricle, and includes an annulus from which leaflets are suspended.The annulus is made up of the confluence of three structures: theatrium, the ventricle, and the leaflets, with the leaflets operablyconnected to papillary muscles (not shown) via chordae tendinae. Thetranslocation device 100 can be deployed to any suitable native valvewithin a heart such as, for example, the mitral valve and/or thetricuspid valve. For example, the translocation device 100 can be mitralvalve translocation device configured to be deployed within the nativemitral valve of a human heart to supplement and/or replace thefunctioning of the native mitral valve. As another example, thetranslocation device 100 can be a tricuspid valve translocation deviceconfigured to be deployed within the native tricuspid valve of a humanheart to supplement and/or replace the functioning of the nativetricuspid valve.

As described herein, during a translocation procedure, one or morenative leaflets are detached from the patient and then reattached to thepatient via the translocation device 100. The one or more nativeleaflets can be detached in any suitable manner, and the location ofdetachment can be any suitable location (e.g., it can vary from onenative leaflet to another). For example, when operating on a nativetricuspid valve, given the proximity of the tricuspid valve toportion(s) of the heart's conduction system, it is important not todisturb and/or damage the conduction system. Accordingly, in someinstances, e.g., to avoid any interruption to the AV node (adjacent thenative septal leaflet), a portion (e.g., about 2 mm to about 4 mm) ofthe native septal leaflet can remain attached to the native annulus,with the remaining portion of the native septal leaflet being detachedtherefrom. In this manner, the operator can avoid trauma to theconduction system. Further, with the portion of the septal leafletremaining attached to the native annulus, the translocation device 100can be secured (e.g., sewn) to the native anatomy without damaging theconduction system.

The translocation device 100 may be sized and/or shaped in any suitablemanner. In some embodiments, the translocation device 100 is annular orring-shaped. In some embodiments the translocation device 100 ispartially, but not completely, annular or ring-shaped. In suchembodiments, for example, the translocation device 100 can besemi-annular such that when implanted it extends circumferentiallyaround a portion of the native annulus, e.g., a portion of the nativeannulus from which a native leaflet has been separated, and does notextend circumferentially around a portion of the native annulus fromwhich a native leaflet remains intact. Regarding a native tricuspidvalve, for example, in some instances, one or two of the three nativeleaflets can be separated from the native annulus and attached to thetranslocation device 100, while the remaining one or two native leafletscan be remain attached to extending from the native annulus; and in someimplementations, the translocation device 100 can be semi-annular suchthat it circumscribes less than the entirety of the circumference of theannulus (e.g., less than 360 degrees). For example, regarding a nativetricuspid valve, in some implementations, the translocation device 100can be semi-annular such that it circumscribes and/or subtends theanterior and posterior leaflets, but not the septal leaflet. This isbecause in a tricuspid valve, although the bases of the anterior andposterior leaflets may dilate, the base of the septal leaflet does not.This is illustrated schematically in FIG. 48 .

Further, each of the three native leaflets of a tricuspid valve formabout 120 degrees of the orifice, or native annulus. Accordingly, insome embodiments, a semi-annular translocation device 100 canapproximate 120 degrees (e.g., if subtending one leaflet) or 240 degrees(e.g., if subtending two leaflets). In various embodiments, thesemi-annular translocation device 100 can approximate any suitabledegrees less than 360 degrees, such as, for example, between about 90and about 120 degrees, between about 120 and about 150 degrees, betweenabout 150 and about 180 degrees, between about 180 and about 210degrees, between about 210 and about 240 degrees, between about 240degrees and about 270 degrees, between about 270 degrees and about 310degrees, and between about 310 degrees and less than 360 degrees, andany suitable sub-ranges therebetween.

As shown in FIG. 2 , the translocation device 100 includes a body 110.The body 110 includes or defines an annulus portion 112 and a leafletportion 114 axially spaced from the annulus portion 112. The annulusportion 112 includes or defines an annulus end 112A that is configuredto be attached to an annulus of a native heart valve after one or morenative leaflets have been separated from the annulus. The leafletportion 114 includes or defines a leaflet end 114A that is configured tobe attached to the native heart valve leaflet(s). With the leaflet end114A attached to the native heart valve leaflet(s) and the annulus end112A attached to the annulus, the native heart valve leaflet(s) arethereby connected to the native heart valve annulus (also referred toherein as “annulus” or “native annulus”).

The body 110 can have any suitable shape and/or size. In someembodiments, the shape and/or size of the body 110 can vary across thebody 110. For example, in some embodiments, the material of the body 110may have a first thickness (i.e., distance between inner and outerdiameter) in a first location, and a second thickness different from thefirst thickness in a second location different from the first location.The material of the body 110 can vary in thickness in any suitablemanner, e.g., it can vary axially and/or circumferentially in anysuitable direction (e.g., from annulus end 112A to leaflet end 144A, orvice versa). In some instances, for example, the thickness of thematerial of the body 110 at its annulus portion 112 can be different(e.g., larger or smaller) than the thickness of the material of the body110 at its leaflet portion 114. In a similar manner, the thickness canvary between the annulus end 112A, the remaining annulus portion 112,the leaflet end 114A, and the remaining leaflet portion 114. In someinstances, for example when translocating a native mitral valve, thebody 110 may have a first thickness at a location configured for theanterior leaflet, and a second thickness less than the first thicknessat a location configured for the posterior leaflet (similar to nativeleaflet thickness differences). As another example, given that nativeheart valve leaflets often vary in thickness, in some embodiments, thebody 110 may have a first circumferential portion having a thicknessapproximately equal to the thickness of a first native leaflet, and asecond circumferential portion having a thickness approximately equal tothe thickness of the second native leaflet. As yet a further example, insome embodiments, the first circumferential portion could have a firstthickness at a location configured to subtend an native anteriorleaflet, and a second thickness, less than the first thickness, at alocation configured to subtend a native posterior leaflet. Further, insome such embodiments, the body 110 may have additional circumferentialportions having other thicknesses, e.g., a circumferential portion to belocated at a commissure could have a thickness less than the thicknessat the location configured to subtend the native anterior leaflet.

As another example, in some embodiments, the body 110 can vary in lengthbetween the annulus end 112A and the leaflet end 114A. In this manner,for example, a first circumferential portion can have a first lengthbetween the annulus end 112A and the leaflet end 114A while a secondcircumferential portion different from the first circumferentiallyportion can have a second length between the annulus end 112A and theleaflet end 114A that is different from the first length (see e.g., FIG.7B).

The body 110 can be formed of any suitable material or combination ofmaterials. In some embodiments, for example, the body 110 is formed ofdecellularized tissue, biological tissue, human pericardial tissue,bovine pericardial tissue, artificial fabric, polymer, and/orpolytetrafluoroethylene.

The body 110 may be configured to simulate proper native valve function,including, for example, maximizing leaflet opening during diastole(i.e., blood flow from atrium to ventricle), and preventing backflow(i.e., from ventricle to atrium) during systole. The native mitralvalve, for example, includes clefts between portions of the posteriorleaflet, providing an increased perimeter and/or circumference, andwhich allow or encourage the posterior leaflet to sufficiently open(e.g., more than they otherwise would) during diastole, and thesegmentation of the posterior leaflet by these clefts allows orencourages each segment to lie flat against the posterior ventricularwall, thereby limiting obstruction to blood flow.

To achieve similar functionality, in some embodiments, the leafletportion 114 of the body 110 has a perimeter that is equal to or largerthan the perimeter of the annulus portion 112. In this manner, theannulus portion 112 (and the annulus end 112A, in particular) can besized (e.g., with a particular perimeter) to attach and/or mate with thenative annulus sufficient to create a fluid-tight seal therebetween(e.g., to prevent leaks around the valve), and the leaflet portion 114(and the leaflet end 114A, in particular) can be sized (e.g., with arelatively similar or larger perimeter) to create a sufficient openingand allow the native leaflets to sufficiently move away from thedesirable blood flow path (e.g., during diastole).

In embodiments in which the perimeter of the leaflet portion 114 islarger than the perimeter of the annulus portion, the relatively largerperimeter of the leaflet portion 114 can be defined or accomplished inany suitable manner. In some implementations, for example, the body 110can be formed with an annulus portion having a fixed perimeter less thana fixed perimeter of the leaflet portion (see e.g., FIG. 6C (top right),with the first edge 212 configured to be the leaflet portion 114 and thesecond edge 214 configured to be the annulus portion 112.

In some implementations, for example, the leaflet portion 114 includesone or more pleats (not shown). The pleat(s) can have an expandableportion (not shown) and a fixed portion (not shown) spaced from theleaflet end 114A. The expandable portion extends to the leaflet end 114Ato define at least partially the relatively larger perimeter of theleaflet end 114A, and the expandable portion is configured to beattached to the native leaflet(s). The pleat(s) are configured to openor unfold (i.e., expand). In some embodiments, the material of the pleatcan be stretchable, e.g., in addition to the pleat(s)′ expandability orability to unfold or open. In some embodiments, the pleat(s) are formedof a material that is not stretchable. Accordingly, the pleat(s) can beexpanded, unfolded, opened, etc., regardless of the nature of thematerial of the pleat, to thereby provide an increased perimeter and/ordiameter. The pleat(s) can not only increase the perimeter, as describedabove, but the pleat(s) can also mimic the natural segmentation (e.g.,provided by clefts) of native valve leaflets, thereby further improvingdiastolic flow. While the leaflet portion 114 having one or more pleatsis described above as providing for a perimeter larger than a perimeterof the annulus portion 112 (when expanded), in some embodiments, theleaflet portion 114 includes one or more pleats to provide for anincreased perimeter (i.e., the leaflet portion 114 has a firstconfiguration with a first perimeter, and a second, expandedconfiguration, with a second perimeter larger than the first perimeter),whereas the increased perimeter is less than or equal to the perimeterof the annulus portion 112. In this manner, a body 110 having a leafletportion 114 with one or more pleats can have a leaflet portion 114perimeter less than, equal to, or greater than, its annulus portionperimeter 112, depending on the particular implementation.

As described in further detail herein, some native leaflets have cleftsor are otherwise characterized as bunched-up or circumferentiallyredundant in configuration. In this manner, when such a native leafletis separated from a native annulus, the native leaflet is allowed tounfurl or circumferentially expand. Upon such expansion, the leaflet endin its unfurled state can, for example, be attached to the expandableportion of the pleat when the expandable portion of the pleat is in itsexpanded configuration.

The leaflet portion 114 can include any suitable number of pleats, e.g.,one pleat, two pleats, three pleats, four pleats, five pleats, sixpleats, or more. In some implementations, the number of pleats can matchthe number of native leaflets to be attached to the leaflet portion 114.For example, when dealing with a native mitral valve, in suchimplementations, a first pleat can be configured to be attached to ananterior native leaflet, and a second pleat can be configured to beattached to a posterior native leaflet. In some implementations, the oneor more pleats can be configured to attach to one native leaflet, whileanother portion of the leaflet portion 114 configured to attach toanother native leaflet can have no pleats. For example, when treating anative mitral valve, in such implementations, a portion of the leafletportion 114 configured to be attached to the posterior leaflet has oneor more pleats, and the portion of the leaflet portion 114 configured tobe coupled to the anterior leaflet has no pleats.

The pleat(s) can have any suitable number of folds, any suitable size,and any suitable thickness, and the expandable portion can expand to anysuitable size. In some implementations, for example, each pleat can addabout 5 mm of perimeter to the expandable portion of the leaflet portion114. So, for instance, three or four pleats can collectively add about15 mm to about 20 mm to the perimeter. In some embodiments, the pleat(s)can fall anywhere within the range of about 2 mm to about 15 mm, whenexpanded.

The pleat(s) can be formed in any suitable manner. In some embodiments,for example, the pleat(s) can be formed by one or more cuts and one ormore rolls and/or folds. For example, the body 110 can be formed of asheet of material, and the sheet of material can be cut and then rolledor folded to create a pleat, as described in further detail herein. Thepleat(s) can be held in place by any suitable technique. For example,the pleat(s) can be sewn in place using suture (e.g., a sterile surgicalsuture composed of polypropylene).

In some embodiments, in addition to or instead of the leaflet portion114 including pleat(s), the leaflet portion 114 can include or defineruffles and/or waves along a portion or the entire circumference of theleaflet portion 114. In this manner, the ruffles and/or waves canprovide similar functionality as the clefts of a native valve. Similarto as described with respect to the pleat(s), the ruffles and/or wavescan be arranged, for example, to be coupled to a posterior nativeleaflet, an anterior native leaflet, or both.

The annulus portion 112 can be sized and configured to be coupled to thenative valve annulus in any suitable manner. In some embodiments, forexample, the annulus portion 112 can be secured to the native valveannulus using sutures. For instance, the sutures can be threaded throughthe annulus end 112A of the annulus portion 112 and through the nativevalve annulus, and then tied off to secure the body 110 to the nativevalve annulus. The sutures can be of any suitable type and size. In someembodiments, for example, the sutures are size 3-0.

In some implementations, the annulus portion 112 is secured to thenative valve annulus using pledgets to limit or prevent any fluid leaksbetween the external surface of the annulus portion 112 and the nativeannulus when the translocation device 200 is secured to the nativeannulus. Any suitable number and arrangement of pledgets can be used,and the pledgets can be formed of any suitable material or combinationof materials. In some embodiments, for example, the pledgets can beformed of a polymer, such as, a polytetrafluoroethylene. In someimplementations, each pledget can be circumferentially distributed witha gap between each pledget (e.g., an interrupted pledegetedconfiguration).

In some embodiments, in addition to or instead of using the pledgets,the annulus end 112A includes or is formed into a collar that isconfigured to promote a fluid-tight seal between the external surface ofthe annulus end 112A or collar and the native annulus when thetranslocation device 100 is secured to the native annulus. In use, thetranslocation device 200 will be subjected to ventricular pressure witheach systole cycle, and so such a collar can limit or prevent leakagecaused by that ventricular pressure around the translocation device 110.In some implementations, the annulus end 112A has a thickness greaterthan a thickness of the remainder of the annulus portion 112, to inpart, promote the fluid-tight seal described above. In some embodiments,the annulus end 112A is formed separately from, and then coupled to, theremainder of the annulus portion 112, while in some embodiments, theannulus end 112A is monolithically or integrally formed with theremainder of the annulus portion 112. In some embodiments, the annulusportion 112 is formed of a sheet of material, and the annulus end ismonolithically or integrally formed with the remainder of the annulusportion 112 with multiple layers of the sheet of material, e.g., to forma collar. In such embodiments, in some implementations, the annulus end112A is formed by rolling the sheet of material.

In some embodiments, the annulus end 112A is or includes a separate ring(e.g., a sewing ring) made from a material (e.g., Dacron) or combinationof materials, and is coupled to the remainder of the annulus portion112. In some implementations, the ring can be rigid or semi-rigid,and/or more rigid than the implementations described above in which theannulus end 112A is formed by rolling the sheet of material.

In some embodiments, the body 110 can include one or more alignmentmarkers to assist an operator (e.g., a surgeon) to align and orient thebody 110 within the native annulus. Similarly, in some instances, thenative valve can be marked before detaching one or more native leaflets,such that the operator can match a marker on the body 110 with a markeron the native anatomy. For example, in some embodiments, the body 110can include four alignment markers circumferentially distributedthereabout, e.g., at 12:00, 3:00, 6:00, and 9:00. The body 110 caninclude any suitable number of alignment markers, in any suitablearrangement. Further, the alignment markers can be formed of anysuitable material. For example, one or more alignment markers can beformed of suture, and/or one or more alignment markers can be formed ofink.

Although various embodiments described herein include a leaflet portionhaving a leaflet end with a perimeter larger than the annulus portionperimeter (and/or the perimeter of the annulus end), in someembodiments, the leaflet portion has a leaflet end having a perimeterequal to the annulus portion perimeter (and/or the perimeter of theannulus end). In yet further embodiments, the leaflet portion has aleaflet end having a perimeter less than the annulus portion perimeter(and/or the perimeter of the annulus end). For example, whentranslocating a native tricuspid valve, in some implementations, theannulus end perimeter configured to be attached to the native annulushas a perimeter greater than the leaflet end perimeter configured to beattached to one or more native leaflets.

FIG. 5A is a flowchart illustrating a method 10 of deploying a valvetranslocation device to a desired location in a body, according to anembodiment. The method 10 includes, at 12, separating a native leafletfrom a native annulus. The separated native leaflet has an annulus edgeat which the native leaflet was joined to the native annulus. The nativeannulus has a leaflet edge at which the annulus was joined to theleaflet edge of the native leaflet.

The method 10 further includes, at 14, attaching to the leaflet edge ofthe native annulus an annulus end of an annulus portion a ring-shapedbody. The annulus end has a perimeter. The method 10 further includes,at 16, attaching to the annulus edge of the native leaflet a leaflet endof a leaflet portion of the ring-shaped body. The leaflet portion isaxially spaced from the annulus portion. The leaflet end has a perimeterlarger than the perimeter of the annulus end.

FIG. 5B is a flowchart illustrating a method 20 of deploying a valvetranslocation device to a desired location in a body, according to anembodiment. The method 20 includes, at 12, separating a native leafletfrom a native annulus. The separated native leaflet has an annulus edgeat which the native leaflet was joined to the annulus and the nativeannulus has a leaflet edge at which the annulus was joined to theleaflet edge of the native leaflet. The method further includes, at 24,attaching to the leaflet edge of the native annulus an annulus end of anannulus portion of a semi-annular body. The method further includes, at26, attaching to the annulus edge of the native leaflet a leaflet end ofa leaflet portion of the semi-annular body. The leaflet portion isaxially spaced from the annulus portion.

The present invention provides devices for treating functional mitralregurgitation and methods of use thereof. The devices translocate asubject's mitral valve in an apical direction. The devices thereby treatmitral regurgitation while preserving a subject's original mitral valveand chordae tendinae.

Translocation Collar Device

Referring now to FIG. 6C, an exemplary translocation collar device 200is depicted. Device 200 comprises a ring-like band of material having anexterior, an interior, a first edge 212, a second edge 214, and a width216 in between. In some embodiments, first edge 212 is configured andshaped to attach to a subject's mitral annulus and second edge 214 isconfigured and shaped to attach to a subject's translocated mitralvalve. In some embodiments, second edge 214 is configured and shaped toattach to a subject's mitral annulus and first edge 212 is configuredand shaped to attach to a subject's translocated mitral valve. Firstedge 212 forms a first opening having an opening diameter. Second edge214 forms a second opening having a second opening diameter.Contemplated dimensions for device 200 include but are not limited tofirst edge 212 having a diameter between about 20 mm and 60 mm, secondedge 214 having a diameter between about 5 mm and 15 mm, and width 216between about 5 mm and 15 mm. The first edge opening and the second edgeopening together form a valvular aperture. In some embodiments, thefirst edge opening diameter is larger than the second edge diameteropening, while in other embodiments the second edge opening diameter islarger than the first edge diameter opening, such that device 200 has asubstantially truncated (e.g., frustum conical-like) conical shape.

Referring now to FIG. 6C, an exemplary translocation collar device 200is depicted. Device 200 can be constructed the same as or similar to,and can function the same as or similar to, any of the valvetranslocation devices described herein. Thus, portions of the device 200are not described in further detail herein. Device 200 includes aring-like band of material having an exterior, an interior, a first edge212 (e.g., a leaflet end of a leaflet portion), a second edge 214 (e.g.,an annulus end of an annulus portion), and a width 216 in between. Insome embodiments, first edge 212 is configured and shaped to attach to asubject's mitral annulus and second edge 214 is configured and shaped toattach to a subject's translocated mitral valve. In some embodiments,second edge 214 is configured and shaped to attach to a subject's mitralannulus and first edge 212 is configured and shaped to attach to asubject's translocated mitral valve, e.g., such that the first edge 212has a perimeter greater than a perimeter of the second edge 214 (towhich the native valve leaflet(s) are attached). First edge 212 forms afirst opening having an opening diameter. Second edge 214 forms a secondopening having a second opening diameter. Contemplated dimensions fordevice 200 include but are not limited to first edge 212 having adiameter between about 20 mm and 60 mm, second edge 214 having adiameter between about 5 mm and 15 mm, and width 216 between about 5 mmand 15 mm. The first edge opening and the second edge opening togetherform a valvular aperture. In some embodiments, the first edge openingdiameter is larger than the second edge diameter opening, while in otherembodiments the second edge opening diameter is larger than the firstedge diameter opening, such that device 200 has a substantiallytruncated (e.g., frustum conical-like) conical shape.

In some embodiments, first edge 212 or second edge 214 is sized to havesubstantially the same diameter as the diameter of a subject's mitralannulus in a dilated condition, while the opposing edge is sized to havesubstantially the same diameter and shape of a subject's normal mitralvalve in an undilated condition. In some embodiments, device 200 isformed from a length of material having width 216 and an arc-shape,wherein an outer edge has a length equal to the circumference of firstedge 212 and an inner edge has a length equal to the circumference ofsecond edge 214, such that the thin band of material can be joinedend-to-end to form the substantially truncated conical shape of device200.

Referring now to FIG. 7A and FIG. 7B, in some embodiments device 200 hasan oblique or slanted truncated cone-like shape, in which first edge 212and second edge 214 are not concentric. For example, while in someembodiments first edge 212 and second edge 214 can be in parallelalignment, in other embodiments first edge 212 and second edge 214 canhave an angle difference that is between about 30 degrees and about 80degrees, such as an angle difference between about 60 degrees and about70 degrees. Device 200 has a variable width 216, thereby forming a firstheight 218 and a second height 220, wherein a first height 218 can begreater, such as in a posteromedial segment. While a symmetrical device200 can be advantageous for subjects having global left ventriculardysfunction that require symmetric displacement of the mitral valve intothe ventricle, a device 200 having an oblique or slanted shape can beadvantageous to treat a subject's particular condition, such as agreater height at a posteromedial portion for inferior ischemicmyopathy.

Referring now to FIG. 8A through FIG. 8C, in some embodiments device 200can further include an annuloplasty ring 222. Annuloplasty ring 222 canbe attached to the interior or exterior of first edge 212, second edge214, or both. In some embodiments, annuloplasty ring 222 can have anasymmetrical shape or non-circular shape sized to fit the anatomy of asubject, as would be understood by those skilled in the art.Annuloplasty ring 222 can have any typical size, such as a size 26, 28,or 30 annuloplasty ring or the like.

Referring now to FIG. 9A through FIG. 9C, in some embodiments device 200can further include concentric folding aligned in parallel with firstedge 212 and second edge 214 along width 216, providing device 200 witha customizable height 224. Device 200200 can be used with unalteredconcentric folding to provide a variable range of movement afterimplantation. A variable range of movement can be advantageous bypermitting device 200 to adapt to varying heart rates. Device 200 canalso have height 224 customized to the dimensions of a subject byplacing a suture or adhesive along the concentric folding, therebyfixing height 224 (FIG. 9C).

Referring now to FIG. 10A through FIG. 10C, in some embodiments device200 can further include one or more sewing cuffs 26. Sewing cuffs 26 canbe attached to the exterior of device 200, to first edge 212, to secondedge 214, or combinations thereof. Sewing cuffs 26 provide device 200with larger and more durable attachment surfaces for suturing to asubject's tissues. In some embodiments, device 200 can further include asmall extension beyond first edge 212 and second edge 214 to increaseattachment surfaces for sutures (e.g., FIG. 47A, 2 mm extensions markedby solid line parallel to annular and apical edges of the collardevice).

Referring now to FIG. 11A through FIG. 11D, in some embodiments device200 includes a rolled sewing cuff or collar 26 on an outercircumference. For example, as shown in FIG. 11A through FIG. 11D, anexemplary device 200 is created using a full template. For demonstrationpurposes, device 200 in FIG. 11A is described with the dimensions of 25mm in depth (width 216), 105 mm in length on an outer arc, and 95 mm inlength on an inner arc. It should be appreciated that device 200 of thepresent invention are not limited to any particular size. In FIG. 11B,the top portion of the template (about 15 mm in depth) (e.g., theannulus portion) is rolled over twice and secured with a running sutureto the body of device 200 to form the sewing cuff or collar 26. Markingson the template and device 200 show quadrants (unbroken lines) andeighth marks (dashed lines), which can be transcribed onto thepericardium of a patient. The completed sewing cuff or collar 26 isshown in FIG. 11C, and the completed frustrum-shaped device 200 is shownin FIG. 11D.

FIG. 12 is a photograph demonstrating the rolled sewing cuff or collar26 of device 200 after it has been completed but before it is ready tobe implanted. Device 200 can then be sewn end-to-end into acylinder/frustrum shape. Markings on device 200 shown quadrants(unbroken lines) and eighth marks (dashed lines). These markingsfacilitate proper orientation and suturing of device 200 to the nativemitral annulus and native mitral valve.

FIG. 13 demonstrates the rolled sewing cuff or collar 26 of device 200ready for suturing. While this is one embodiment, there are many otherembodiments; device 200 could be constructed by attaching a sewing cuff226 to the main body of device 200. Sewing cuff 226 can be made of anymaterial, such as a Dacron sewing ring similar to that which is seen oncommercially available replacement valves, to which device 200 would beattached. While the rolled sewing cuff or collar 26 may be flexible,there may be situations in which the sewing cuff 226 would be semirigidor rigid. The rolled edge serves as a gasket to seal the outer sutureline, which is subject to ventricular pressure with each systole.

In some embodiments, suturing of device 200 can be enhanced using aninterrupted pledgeted horizontal mattress suture line using relativelysmall pledgets (FIG. 14 ). While typical mitral valve replacement isdone using similar sutures, usually 12-14, device 200, in someimplementations benefits from using smaller (e.g., 7 mm×3 mm×1.5 mm,firm) Teflon pledgets and to place 20 or more total pledgeted sutures asshown in FIG. 14 . Use of a smaller number of large pledgets, in someinstances, leads to constriction/decreased diameter of the outer sutureline. In some embodiments, the use of a rigid or semi-rigid sewing ringcan allow for fewer pledgets to be placed, more similar to typicalmitral valve replacements. In some embodiments, the rolled outer edge ofdevice 200 is flexible and provides two advantages. A flexible device200 facilitates sliding device 200 down into the annulus prior tosuturing (i.e., the surgeon slides device 200 down over all thesutures), which is in contrast to a stiff/rigid sewing ring (like astandard prosthetic replacement valve) which is oftentimes difficult toplace into the annulus. A flexible device 200 may also better preserveannular motion (the normal mitral annulus expands and contracts duringthe cardiac cycle) and may also better preserve ventricular function atthe base of the heart (which can be compromised after insertion of aconventional rigid annuloplasty ring or a mitral prosthesis).

FIG. 15 demonstrates device 200 mounted on a rigid circular holder inorder to facilitate suturing of device 200. In this example a mitralannuloplasty ring is being used as the rigid circular holder. Additionalholder styles may be circular in shape. However, as the translocationprocedure does not incorporate annuloplasty, the holder ring is removedprior to implantation (see FIG. 16 through FIG. 18 ). Sutures are placedas shown in FIG. 15 (and in typical fashion for a conventional mitralvalve replacement) with the pledget on the atrial surface of the annulusand the sutures emerging on the ventricular side of the annulus. Theyare then placed in the rolled sewing cuff or collar 26 of device 200.While various suture sizes can be used, size 3-0 sutures are of optimalsize in some implementations. Device 200 in FIG. 12 has been evertedfrom its final position in a patient. Once the sutures are placedthrough the rolled edge, device 200 is lowered into position, the holdersutures on the holder divided, and the holder removed. At this point,device 200 is inverted back into the ventricle, the outer sutures tied,and the native mitral leaflets can be sewn to the free edge (e.g.,leaflet end of leaflet portion) at the bottom of device 200.

Sizing of device 200 is now described. The circumference of the nativemitral valve annulus can be measured using any suitable technique,including for example, transesophageal echocardiography (TEE) duringmid-diastole; typically patients with secondary MR have circumferencesbetween 100 and 140 mm. Device 200 sizes implanted range between 70 mmouter circumference (60 mm inner circumference) and 105 mm outercircumference (95 mm inner circumference), with the most commonly chosensize being 105×95 mm. Device 200 can, in some embodiments, for example,have a constant length (referred to as the width of device 200), such as10 mm for example, between the outer and inner circumference (e.g., 150mm by 95 mm), while in some embodiments the length (width) between theouter and inner circumference can be vary. In some such embodiments, forexample, device 200 can be wider in some locations (e.g., the anteriorleaflet aspect) than in others (e.g., the posterior leaflet portion).

Geometries of device 200 are now described. In order to simulate thenative mitral valve function and to maximize leaflet opening duringdiastole, it is important to maximize the diameter of the inner sutureline (e.g., the leaflet end of the leaflet portion). In someembodiments, the circumference and/or the diameter of the inner sutureline is larger than that of the outer suture line (e.g., the annulus endof the annulus portion). In order to achieve this goal, anotherembodiment of the present invention includes one or more pleats in theportion of device 200 that subtends the posterior leaflet (e.g., theleaflet portion). As an example implementation, each pleat can add 5 mmof circumference to the inner suture line. Device 200 can include anysuitable number of pleats. In an exemplary embodiment, device 200includes 3 to 4 total pleats. In aggregate, using the example of eachpleat adding 5 mm of circumference, the 3 to 4 pleats adds 15 to 20 mmto the circumference of the inner suture line. In some embodiments,device 200 can include multiple pleats, with one or more of the pleatsbeing different in size; e.g., a first pleat can add 4 mm ofcircumference and a second pleat can add 6 mm of circumference.Additional embodiments of device 200 can include more than 4 pleats orcan add length to the inner suture line by creating a ruffle or waveeffect along device 200. Pleats, ruffles, and/or waves can be placed oneither the anterior, posterior, or both leaflets. The native mitralvalve is characterized by “clefts” between portions of the posteriorleaflet (FIG. 19 ), which allow the posterior leaflet to open maximallyduring diastole (when blood flows from the atrium to the ventricle) andin fact the segmentation of the posterior leaflet by these clefts allowseach segment to lie flat against the posterior ventricular wall andcause a minimum amount of obstruction to blood flow. The pleats servethe dual function of increasing the overall circumference of the innersuture line to create a larger opening in diastole and of mimicking the“segmentation” of the native posterior leaflet to contribute to improveddiastolic flow.

The progression of the creation of device 200 with pleats 215 is shownin FIG. 20A through FIG. 20H. The starting full template is shown inFIG. 20A. For demonstration purposes, device 200 in FIG. 20A isdescribed with the dimensions of 25 mm in depth, 105 mm in length on anouter arc, and 95 mm in length on an inner arc. It should be appreciatedthat device 200 is not limited to any particular size. The top portionof the template (15 mm in depth) is rolled over twice to form the sewingcollar, leaving about 10 mm below the collar to form the depth of device200. Markings on the template and device 200 show the location of eachplate (X-marks) and the location of the center of device 200 to beplaced at the center of the anterior leaflet (dashed line). Pleat 15location “X” is the portion of the plate on the sewing collar and ‘x’ isthe portion on device 200 proper. The “X” portion on the sewing collaris cut out (FIG. 20B), while the ‘x’ portion on device 200 is sewntogether using a running suture (FIG. 20C) to form a pleat 15 (FIG.20D). The sewing collar is then rolled twice and stitched down with arunning suture (FIG. 20E). Next, figure-of-eight stitches are placed inthe sewing collar at the locations where the pleats 215 were formed toensure no leakage from the collar (FIG. 20F). This embodiment is alsoapplicable to the translocated tricuspid. The completed pleated device200 is shown in FIG. 20G; the completed frustrum-shaped device 200 isshown in FIG. 20H.

While pleats 215 are described for demonstration purposes to be 5 mm insize, they can be smaller or larger as needed (e.g., 2 to 15 mm). Thenumber of pleats 215 can vary between 2 to 6 or more, for example. Thelength of the inner suture line can increased using alternative methods,such as by ruffling device 200 instead of or in addition to creatingdistinct pleats 215 (FIG. 20I). Markers (either suture or colored marks)can be placed on device 200 at the 12 o'clock, 3 o'clock, 6 o'clock, and9 o'clock positions, and/or other suitable locations. These markers helpa surgeon to sew and align the inner suture line with the native valve,which are marked respectively at similar locations prior to be detachedfrom its native annulus. While the depth of device 200 below the sewingcollar is described for demonstration purposes to be about 10 mm, anexemplary device 200 can have a depth of between about 5 mm to 25 mmdepending on a patient's geometry. In some embodiments, device 200 caninclude a few extra millimeters of depth (about 1 to 3 mm) on the innersuture line portion in order to provide room to attach the inner sutureline (marked in FIG. 21 ).

FIG. 22A depicts a completed pleated device 200 (having 4 pleats 215)mounted to a mitral valve replacement sizer (left) and unmounted (right)showing the ‘anterior leaflet’ portion, wherein device 200 is prototypedusing surgical drape material. FIG. 22B depicts a prototype device 200mounted to a mitral valve sizer (left) and unmounted (middle, right)showing ‘posterior leaflet’ portion with pleats 215. FIG. 22C depictsadditional views of the unmounted device 200 from the atrial/annularside (left) and the ventricular/leaflet side (right).

The translocation devices of the present invention can be constructedfrom any material suitable for implanting, including but not limited tobiocompatible polymers, fabrics, plastics, metals, as well as biologicaltissue such as autografts, allografts, xenografts, and engineered tissueconstructs, and combinations thereof. Exemplary materials includeDacron® cloth (flexibility modified by albumin coating),gluteraldehyde-fixed bovine pericardium, a subject's native pericardium,and the like.

In some embodiments, the devices are made from autologous pericardiumtreated with 0.625% glutaraldehyde for 2-3 minutes then rinsed withsaline. The devices can also be made from bovine or other animal tissuepericardium. Bovine pericardium (usually treated with glutaraldehyde) iswidely used for valvular replacement prostheses and for intracardiac andintravascular patching. The devices can also have a varied thickness.For example, the portion of the devices that subtends the nativeanterior mitral valve leaflet can be thicker (such as the typicalthickness of native anterior leaflet) and the portion that subtends theposterior leaflet can be thinner (to replicate the native leaflet, whichis thinner than the anterior leaflet).

Materials including tissue can be can be treated with a sterilizationstep. The sterilization step can apply any suitable sterilizationmethod, including but not limited to radiation (e.g., gamma radiation,x-ray radiation, ultraviolet sterilization, and electron beamprocessing), gaseous formaldehyde, carbon dioxide, ozone, ethyleneoxide, peracetic acid, ethanol, hydrogen peroxide, and the like. Thetissue can be provided with original cells, completely decellularized,or decellularized and reseeded with host cells. In some embodiments, thetissue can be enhanced with one or more additives, including but notlimited to one or more additional extracellular matrix material and/orblends of naturally occurring extracellular matrix material, such ascollagen, fibrin, fibrinogen, thrombin, elastin, laminin, fibronectin,vitronectin, hyaluronic acid, chondroitin 4-sulfate, chondroitin6-sulfate, dermatan sulfate, heparin sulfate, vixapatin (VP12), heparin,and keratan sulfate, proteoglycans, and combinations thereof. Theadditives can include natural peptides, such asglycyl-arginyl-glycyl-aspartyl-serine (GRGDS), arginylglycylasparticacid (RGD), and amelogenin. In some embodiments, the additives caninclude nutrients, such as bovine serum albumin. In some embodiments,the additives can include vitamins, such as vitamin B2, vitamin Ad,Vitamin D, Vitamin E, and Vitamin K. In some embodiments, the additivescan include nucleic acids, such as mRNA and DNA. In some embodiments,the additives can include natural or synthetic steroids and hormones,such as dexamethasone, hydrocortisone, estrogens, and its derivatives.In some embodiments, the additives can include growth factors, such asfibroblast growth factor (FGF), transforming growth factor beta (TGF-β),and epidermal growth factor (EGF). In some embodiments, the additivescan include a delivery vehicle, such as nanoparticles, microparticles,liposomes, viral and non-viral transfection systems. The additives caninclude one or more therapeutics. The therapeutics can be natural orsynthetic drugs, including but not limited to: analgesics, anesthetics,antifungals, antibiotics, anti-inflammatories, nonsteroidalanti-inflammatory drugs (NSAIDs), anthelmintics, antidotes, antiemetics,antihistamines, anticancer drugs, antihypertensives, antimalarials,antimicrobials, antipsychotics, antipyretics, antiseptics,antiarthritics, antituberculotics, antitussives, antivirals,cardioactive drugs, cathartics, chemotherapeutic agents, a colored orfluorescent imaging agent, corticoids (such as steroids),antidepressants, depressants, diagnostic aids, diuretics, enzymes,expectorants, hormones, hypnotics, minerals, nutritional supplements,parasympathomimetics, potassium supplements, radiation sensitizers, aradioisotope, fluorescent nanoparticles such as nanodiamonds, sedatives,sulfonamides, stimulants, sympathomimetics, tranquilizers, urinaryanti-infectives, vasoconstrictors, vasodilators, vitamins, xanthinederivatives, and the like.

Kits

The present invention also encompasses surgical kits for translocating avalve. The kits can include one or more translocation devices, whereineach device has the same size and thickness or a range of sizes andthicknesses to be selected by a surgeon to fit within a subject. Thekits can further include one or more instruments relevant to thetranslocation procedure, including but not limited to: suture needles,suture thread, suture pledgets, forceps, scissors, scalpels,translocation device holders, and the like. In some embodiments, thekits can further include one or more tools to measure portions of asubject's heart and to select dimensions of a translocation device, suchpurpose-built sizers to measure a subject's native annulus and mitralvalve circumference. In some embodiments, the kits can further includeinstructions for using a 3D echocardiogram to perform the measurements.For example, a 3D echocardiogram may be performed prior to an operationand a 3D analysis system may perform “in-silico” modeling to determinethe optimal dimensions of a translocation device.

In some embodiments, the kit may also include other tools that furthertreat FMR. For example, the kit may include a circumferential band 228configured to bring the papillary muscles closer together, such as byplacing circumferential band 228 around the papillary muscles (FIG. 23). In another example, the kit may include one or more tethers or chords230 configured to increase and maintain the apical length ordisplacement of an implanted device 200 (FIG. 24 ). Tethers or chords230 can be attached to the papillary muscles at one end and to apicaledge 214 of device 200 or to a large pledget secured to the epicardiumof the heart. Tethers or chords 230 can be constructed from ePTFEsutures, such as sutures that are commonly used for repair ofdegenerative mitral regurgitation. In another example, the kit mayinclude additional cuffs 26 attachable to device 200 and configured tofurther reduce the opening diameter of first edge 212 or second edge214. Cuffs 26 each have a cuff aperture and an outer diameter thatattaches, such as by suturing, to first edge 212 or second edge 214 ofdevice 200, and the subject's anatomy can be sutured to the cuffaperture.

Methods of Valve Translocation

The present invention further includes methods of using thetranslocation collar devices of the present invention. Referring now toFIG. 25 , an exemplary method 300 is depicted. Method 300 begins withstep 302, wherein a translocation collar device of the present inventionis provided, the collar device having a ring-like shape with an annularedge (e.g., annulus end), an apical edge (e.g., leaflet end), and awidth (e.g., distance from annulus end to leaflet end) in between. Instep 304, a circumferential incision is formed around a perimeter of avalve to separate a valve annulus from a valve perimeter. The incisionkeeps the structure of the original valve leaflets, commissures, andother physical features intact, including the chordae tendinae andassociated muscles (FIG. 26A through FIG. 26C). In step 306, the annularedge of the collar device is circumferentially attached to the valveannulus. In step 308, the apical edge of the collar device iscircumferentially attached to the valve perimeter (FIG. 26D, FIG. 26E).The attachment means can include sutures, adhesives, staples, and/or thelike.

In some embodiments, a method for implanting the translocation collardevice begins after sizing the device, as discussed herein. The methodincludes marking four regions (i.e., quadrants) of a patient's mitralvalve annulus to prevent rotation of the valve leaflets relative to theannulus during the suturing process. The valve is separated from theannulus in the quadrants. For each quadrant, multiple (e.g., about threeor more) horizontal mattress sutures are placed between the device andthe annulus and additional (e.g., about three or more) horizontalmattress sutures are placed between the device and the valve leaflets.These sutures allow the device to be seated below the plane of theannulus and the leaflets. Each quadrant is sutured with a runningsuture, and the method is repeated for all four quadrants. In someembodiments, less or more than four regions can be used.

In some embodiments, the dimensions of the valve are sized before atranslocation collar device is provided. In one embodiment, thedimensions are sized by measuring the native annulus aftercircumferential incision and detachment of the valve with a first set ofsizers, and measuring the circumference of the valve perimeter with asecond set of sizers. In some embodiments, the dimensions are sized bymeasuring the heart with a 3D echocardiogram and analyzing themeasurement with a 3D analysis system.

In some embodiments, first edge 212 or second edge 214 is sized to asubject's annulus. The dimensions of the opposing edge can be determinedin reference to the size of the subject's annulus. First edge 212 orsecond edge 214 can be reduced or “downsized,” such as by one or moresizes. For example, the size can be reduced by 2 sizes (in which 1size=5 mm circumference). For reference, a common size is 38 (orificearea of about 722 mm², circumference of about 95 mm). The smallerorifice would then be size 34 (apical opening area of about 572 mm²,circumference of about 85 mm). These can be labeled as small, medium,large, and the like, in which a surgeon uses sizers to determine whetherthe annulus of a patient is small, medium, large, and the like. Eachsize can be based on the sizer, and the opposing edge can be downsizedby the circumference, such as by 10 mm.

In some embodiments, the valve annulus and valve perimeter are fullyseparated prior to attaching the collar device. In some embodiments, thevalve annulus and valve perimeter are partially separated, and thecollar device is attached as the circumferential incision is made in astepwise sequence. A stepwise sequence can be advantageous in that thevalve annulus and valve perimeter are always attached together, eitherby natural tissue or by the collar device, improving valve stabilitythroughout the operation. In some embodiments, a portion less than theentirety of the valve annulus/perimeter can be separated, and asemi-annular collar device can be attached to the portion (e.g., asubset of native leaflets can be removed, while one or more nativeleaflets remain attached to the native annulus.

Referring now to FIG. 27 and depicted in FIG. 28 through FIG. 38 ,another exemplary method 400 is shown, wherein method 400 is configuredto facilitate durable mitral valve repair for many patients andphysicians. The method includes step 402 of forming a patch (implant, asdescribed above; see FIG. 28 ). In some implementations, step 402further includes marking regions (e.g., quadrants) and forming an outerring portion (e.g., folding the patch). The method can further includestep 404 of forming a ring configured to stiffen the patch (FIG. 29 ).The ring can be elliptical, circular-like, or have other shapes intendedto adapt the patch to a shape of the mitral valve. The ring can havevarious stiffnesses depending on the materials (e.g., of the patch andsutures) and size and condition of the patient, etc. Furthermore, thering can include an extension leg configured to ease handling andmaneuvering of the ring, such as when performing the method. Theextension leg can be integrally formed to the ring or configured tocouple to the ring.

The method further includes step 406 of coupling the ring and the patch(FIG. 30A and FIG. 30B). In some embodiments, this includes insertingthe ring and the outer ring portion of the patch. For example, couplingthe ring can substantially enclose the ring within an outer portion ofthe patch. In some embodiments, at least one of the patch and/or ringcan include markings to orient and align the patch and/or ring. In someembodiments, the method includes securing the ring within the outerportion of the patch with sutures (which may be permanent or temporary),such as by closing ends of the outer portion.

In some embodiments, the method further includes step 408 of detachingleaflet tissue from valve tissue within the heart (e.g., using typicalmethods) prior to attaching a first end of sutures to the valve tissue(FIG. 31A and FIG. 31B). Furthermore, the method can include step 410 ofcoupling sutures to the patch (FIG. 32 ), such as by passing a secondend of the sutures through an inner portion of the patch. The patch canbe further positioned adjacent to the valve tissue and tightening thesutures (i.e., removing slack in the sutures). For example, positioningthe patch adjacent to the valve tissue can include sliding the patchalong the sutures to be adjacent to the first end of the sutures (FIG.33A, FIG. 33B). In some embodiments, the method further includessecuring the patch to the valve tissue (FIG. 34 through FIG. 38 ). Forexample, the securing of the patch can include tying-off the sutures andremoving excess suture material (FIG. 36 ).

The method can further include step 412 of coupling valve tissue to thepatch and/or leaflet tissue to the inner portion of the patch. Forexample, coupling the leaflet tissue can include placing sutures betweenthe leaflet tissue and the inner portion. Furthermore, in someembodiments the method can further include step 414 of removing excessmaterial, such as the ring (e.g., such as by the extension leg). In someembodiments, only the extension leg is removed. In some embodiments, anytemporary sutures are removed.

In some embodiments, the methods of the present invention are performedpercutaneously. The collar device can be introduced near the valve site,such as in a ventricle or atrium, using a transapical technique, atransfemoral technique, a transaortic technique, a transseptaltechnique, and the like to implant the collar device in acircumferential fashion around a subject's normal valve annulus.

EXPERIMENTAL EXAMPLES

The invention is further described in detail by reference to thefollowing experimental examples. These examples are provided forpurposes of illustration only, and are not intended to be limitingunless otherwise specified. Thus, the invention should in no way beconstrued as being limited to the following examples, but rather, shouldbe construed to encompass any and all variations which become evident asa result of the teaching provided herein.

Without further description, it is believed that one of ordinary skillin the art can, using the preceding description and the followingillustrative examples, make and utilize the present invention andpractice the claimed methods. The following working examples therefore,specifically point out exemplary embodiments of the present invention,and are not to be construed as limiting in any way the remainder of thedisclosure.

Example 1: In Vivo Swine Analysis

There is no reliable and durable mitral valve repair option for patientswith functional mitral regurgitation (FMR). Existing devices (tissue ormechanical) and methods are not durable, suffer high recurrence rates,and are limited by increased risk of bleeding, prosthetic valvedysfunction, infection, and thromboembolism (FIG. 39 ). The presentstudy aims to improve upon valve repair by examining the efficacy ofvalve translocation collars.

Yorkshire swine (50-70 kg) were placed on cardiopulmonary bypass fortranslocation patch repair (n=7). Inner patch diameter was sized toanterior mitral valve leaflet. Leaflet was detached from the annulus andthe bovine pericardial patch was sewn in. Pre- and post-operativeechocardiography were used to evaluate efficacy of patch (FIG. 40A).

The collar implants improved coaptation from 0-4 mm to 6-10 mm (FIG.40B). Other areas of improvement include: improved predictors of repairdurability; tenting area reduced; leaflet angles improved. Mild sutureline regurgitation was observed in 3/7 swine. Mitral valve area afterrepair was about 2.3 cm² (normally 5 cm²).

Modifications were made to reduce or prevent suture line regurgitation.The outer diameter of the collar implant is sized to fit the dimensionsof the patient's annulus, forming a smaller patch diameter having a moreacute patch angle (FIG. 42A). Locking sutures are used to preventcrimping (FIG. 45A, FIG. 45B). 2 mm tabs were added to the upper andlower edges of the collar to improve suturing, and horizontal mattresssutures were used to seat the collar below the annulus/leaflet (FIG. 46Athrough FIG. 47D).

The disclosures of each and every patent, patent application, andpublication cited herein are hereby incorporated herein by reference intheir entirety. While this invention has been disclosed with referenceto specific embodiments, it is apparent that other embodiments andvariations of this invention may be devised by others skilled in the artwithout departing from the true spirit and scope of the invention. Theappended claims are intended to be construed to include all suchembodiments and equivalent variations.

While various embodiments have been described above, it should beunderstood that they have been presented by way of example only, and notlimitation. Where methods described above indicate certain eventsoccurring in certain order, the ordering of certain events may bemodified. Additionally, certain of the events may be performedconcurrently in a parallel process when possible, as well as performedsequentially as described above.

Where schematics and/or embodiments described above indicate certaincomponents arranged in certain orientations or positions, thearrangement of components may be modified. While the embodiments havebeen particularly shown and described, it will be understood thatvarious changes in form and details may be made. Any portion of theapparatus and/or methods described herein may be combined in anycombination, except mutually exclusive combinations.

The embodiments described herein can include various combinations and/orsub-combinations of the functions, components, and/or features of thedifferent embodiments described. Various of the above-disclosed andother features and functions, or alternatives thereof, may be combinedinto many other different systems or applications. Various presentlyunforeseen or unanticipated alternatives, modifications, variations, orimprovements therein may be subsequently made by those skilled in theart, each of which is also intended to be encompassed by the disclosedembodiments.

What is claimed is:
 1. An apparatus comprising: a ring-shaped bodydefining an annulus end, a leaflet end, and a length running from theannulus end to the leaflet end, the ring-shaped body having an annulusportion at the annulus end and a leaflet portion at the leaflet end,axially spaced from the annulus portion; the annulus portion having aperimeter and being configured to be attached to an annulus of a nativeheart valve from which a leaflet of the native heart valve has beenseparated; and the leaflet portion having a perimeter equal to or largerthan the annulus portion perimeter and being configured to be attachedto the separated native heart valve leaflet and thereby to connect theseparated native heart valve leaflet to the native heart valve annulus;the ring-shaped body including a pleat parallel to the length, the pleathaving an expandable portion extending to the leaflet end of thering-shaped body to define in part the perimeter of the leaflet end, anda fixed portion spaced from the leaflet end, the expandable portion ofthe pleat being configured to be attached to the separated native heartvalve leaflet.
 2. The apparatus of claim 1, wherein: the pleat is afirst pleat; the expandable portion of the first pleat is configured tobe attached to the separated native heart valve leaflet; the leafletportion of the ring-shaped body includes a second pleat having anexpandable portion extending to the leaflet end of the ring-shaped bodyfurther to define in part the perimeter of the leaflet end and a fixedportion spaced from the leaflet end, the expandable portion of thesecond pleat being configured to be attached to the separated nativeheart valve leaflet.
 3. The apparatus of claim 1, wherein: the leafletend of the ring-shaped body has a first circumferential portion having athickness and a second circumferential portion have a thicknessdifferent from the thickness of the first circumferential portion. 4.The apparatus of claim 3, wherein: the separated native heart valveleaflet is a first leaflet from a plurality of native heart valveleaflets that have been separated from the native heart valve and; thefirst leaflet having a first thickness and a second leaflet from theplurality of native heart valve leaflets having a second thickness, thefirst thickness being greater than the second thickness.
 5. Theapparatus of claim 4, wherein the native heart valve is a mitral valve,the first leaflet is an anterior leaflet and the second leaflet is aposterior leaflet.
 6. The apparatus of claim 1, wherein the annulus endhas a thickness greater than a thickness of the remainder of the annulusportion.
 7. The apparatus of claim 6, wherein the annulus portion isformed of a sheet of material, the annulus end is integrally formed withthe remainder of the annulus portion with multiple layers of the sheetof material.
 8. The apparatus of claim 7, wherein the annulus end isformed by rolling the sheet of material.
 9. The apparatus of claim 6,wherein the annulus end is formed separately from, and coupled to, theannulus portion.
 10. The apparatus of claim 1, wherein the ring-shapedbody is formed of biological tissue.
 11. The apparatus of claim 10,wherein the biological tissue is human or bovine pericardial tissue. 12.The apparatus of claim 1, wherein the ring-shaped body is formed of atleast one of decellularized tissue, polymer, or artificial fabric. 13.The apparatus of claim 1, wherein the annulus portion has a thicknessdifferent from the leaflet portion.
 14. An apparatus comprising: aring-shaped body defining an annulus end, a leaflet end, and a lengthrunning from the annulus end to the leaflet end, the ring-shaped bodyhaving an annulus portion at the annulus end and a leaflet portion atthe leaflet end, axially spaced from the annulus portion; the annulusportion being configured to be attached to an annulus of a native heartvalve from which a leaflet of the native heart valve has been separated,the leaflet portion including a pleat parallel to the length, the pleathaving an expandable portion extending to the leaflet end and a fixedportion spaced from the leaflet end, the expandable portion of the pleatbeing configured to be attached to the separated native heart valveleaflet and thereby to connect the separated native heart valve leafletto the native heart valve annulus.
 15. The apparatus of claim 14,wherein the expandable portion of the pleat has a first configuration inwhich the leaflet end has a first perimeter and a second, expandedconfiguration, in which the leaflet end has a second perimeter greaterthan the first perimeter.
 16. The apparatus of claim 15, wherein theannulus end has a perimeter, and the leaflet end has a perimeter equalto or greater than the annulus end perimeter when the expandable portionof the pleat is in its second, expanded configuration.
 17. The apparatusof claim 15, wherein the annulus end has a perimeter, and the leafletend has a perimeter less than the annulus end perimeter when theexpandable portion of the pleat is in its second, expandedconfiguration.
 18. The apparatus of claim 14, wherein the leaflet end ofthe ring-shaped body has a first circumferential portion having athickness and a second circumferential portion having a thicknessdifferent from the thickness of the first circumferential portion. 19.The apparatus of claim 14, wherein the annulus end has a thicknessgreater than a thickness of the remainder of the annulus portion.
 20. Anapparatus comprising: a ring-shaped body having an annulus end, aleaflet end and a length therebetween, wherein the length defines anannulus portion adjacent to the annulus end and a leaflet portionadjacent to the leaflet end and axially spaced from the annulus portion;the annulus end having a perimeter and being configured to be attachedto an annulus of a native heart valve from which a leaflet of the nativeheart valve has been separated; the leaflet end having a perimeterlarger than the annulus end perimeter and being configured to beattached to the separated native heart valve leaflet and thereby toconnect the separated native heart valve leaflet to the native heartvalve annulus; and at least one expandable pleat within the leafletportion of the ring-shaped body length, wherein the at least oneexpandable pleat runs perpendicular to the leaflet end perimeter.